Download Swine Influenza A (H1N1 Virus): A Pandemic Disease

Review Article
Swine Influenza A (H1N1 Virus): A Pandemic Disease
Gangurde HH, Gulecha VS, Borkar VS, Mahajan MS, Khandare RA, Mundada AS
Department of Pharmaceutics, SNJB’s SSDJ College of Pharmacy, Neminagar, Chandwad, Nasik, Maharashtra, India
A R T I C L E
I N F O
Article history:
Received 9 September 2009
Accepted 18 September 2009
Available online 19 October 2011
Keywords:
Coughing
Fever
H1N1
sore throat
swine flu
swine influenza virus
A B S T R A C T
Swine influenza (SI) is a respiratory disease of pigs caused by type A influenza that regularly
causes pandemics. SI viruses do not normally infect humans; however, human infections with
SI do occur, and cases of human-to-human spread of swine flu viruses have been documented.
Swine influenza also called as swine flu, hog flu, and pig flu that refers to influenza is caused by
those strains of influenza virus, called SI virus (SIV), that usually infect pigs endemically. As of
2009, these strains are all found in influenza C virus and subtypes of influenza A virus known as
H1N1, H1N2, H3N1, H3N2, and H2N3. The viruses are 80–120 nm in diameter. The transmission of
SIV from pigs to humans is not common and does not always cause human influenza, often only
resulting in the production of antibodies in the blood. The meat of the animal poses no risk of
transmitting the virus when properly cooked. If the transmission does cause human influenza, it
is called zoonotic swine flu. People who work with pigs, especially people with intense exposures,
are at an increased risk of catching swine flu. In the mid-20th century, the identification of influenza
subtypes became possible; this allowed accurate diagnosis of transmission to humans. Since then,
50 confirmed transmissions have been recorded; rarely these strains of swine flu can pass from
human to human. In humans, the symptoms of swine flu are similar to those of influenza and of
influenza-like illness, namely, chills, fever, sore throat, muscle pains, severe headache, coughing,
weakness, and general discomfort. Influenza A is a single-stranded RNA virus with eight different
segments. When two viruses co-infect the same cell, new viruses can be produced that contain
segments from both parental strains.
Introduction
Swine influenza (SI) is a virus disease that can cause epidemics
of acute respiratory disease in pigs. The disease is due to viruses
from the type A of the Orthomyxoviridae family, (there are three
types in the Orthomyxoviridae family: A, B, and C). The etiology of SI
is complex according to the high genetic variation of the causative
viruses, mainly on the basis of two glycoproteins: hemagglutin
(H) and neuramidase (N). The nomenclature for virus designation
Access this article online
Quick Response Code:
Website: www.sysrevpharm.org
DOI: 10.4103/0975-8453.86300
Correspondence:
Hemant H Gangurde; E-mail: [email protected]
110
has been established by the World Health Organization (WHO) in
1980. The disease causes high morbidity but low mortality. It can
also persist as an endemic infection and is a potential zoonosis.[1-6]
The 2009 flu outbreak in humans, known as “swine flu,” is due to
a new strain of influenza A virus subtype H1N1 that contains genes
closely related to SI.[7] The origin of this new strain is unknown.
Influenza A virus subtype H1N1 is an epidemic of a new strain of
influenza virus commonly referred to as “swine flu.” It is thought to
be a mutation (“reassortment”) of four known strains of influenza
A virus subtype H1N1: one endemic in humans, one endemic in
birds, and two endemic in pigs (swine). The source of the outbreak
in humans is still unknown, but cases were first discovered in the
United States and soon after in Mexico, which had a surge of cases,
many of them fatal.[8]
H1N1 and H3N2 swine flu viruses are endemic among pig
populations in the United States and something that the industry
deals with routinely. Studies have shown that the swine flu H1N1
virus is common throughout pig populations worldwide, with 25%
of animals showing antibody evidence of infection. In the United
States, studies have shown that 30% of the pig population has
antibody evidence of having had H1N1 infection. More specifically,
51% of pigs in the north-central United States have been shown to
have antibody evidence of infection with the swine H1N1 virus.
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
Human infections with swine flu H1N1 viruses are rare. There is
currently no way to differentiate antibodies produced in response
to flu vaccination in pigs from antibodies made in response to pig
infections with swine H1N1 influenza. While H1N1 swine viruses
have been known to circulate among pig populations since at least
1930, H3N2 influenza viruses did not begin circulating among US
pigs until 1998. The H3N2 viruses initially were introduced to the
pig population by humans. The current swine flu H3N2 viruses are
closely related to human H3N2 viruses.
Swine flu outbreaks in pigs occur regularly, causing high levels of
illness and low death rates. Swine influenza viruses may circulate
among swine throughout the year, but most outbreaks occur during
the late fall and winter months similar to outbreaks in humans. Swine
flu occasionally infects people without causing large outbreaks. Like
all influenza viruses, swine flu viruses change constantly. Pigs can
be infected by bird and human influenza viruses as well as swine
influenza viruses. When influenza viruses from different species
infect pigs, the viruses can reassort (i.e., swap genes) and new
viruses can emerge. That is what has happened with the recent
cases of H1N1. This form of the H1N1 swine flu virus has never
been seen before, and it is also causing illness among humans in
many countries. It is a genetic mixture of viruses from pigs, birds,
and people. Because it is a new virus, most people’s immune
systems do not know how to fight this H1N1 virus. So, many people
are susceptible to becoming ill. A variant of H1N1 caused the flu
pandemic of 1918.[9-17]
Based on its genetic structure, the new virus is without question
a type of swine influenza, derived originally from a strain that lived
in pigs.[18] This origin was largely used by mass media in the first
days of the epidemic. Despite this origin, the current strain is now
a human-to-human transmitted virus, requiring no contact with
swine. WHO stated that no pigs in any country had been determined
to have the illness, but farmers remain alert due to concerns that
infected humans may pass the virus to their herds.[19] On May 2, 2009,
it was announced that a Canadian farm worker who had traveled
to Mexico had transmitted the disease to a herd of pigs, showing
that the disease can still move between species.[20] Some authorities
object to calling the flu outbreak “swine flu.” US Agriculture
Secretary Tom Vilsack expressed concerns that this would lead to
the misconception that pork is unsafe for consumption.[21] Centers
for Disease Control and Prevention (CDC) now refers it as novel
influenza A (H1N1).[22] In the Netherlands, it was originally called
“pig flu,” but is now called “Mexican flu” by the national health
institute and the media. South Korea and Israel briefly considered
calling it the “Mexican virus.”[23] Currently, the South Korean press
uses “SI,” short for “swine influenza.” Taiwan suggested the names
“H1N1 flu” or “new flu,” which most local media now use.[24] The
World Organization for Animal Health has proposed the name “North
American influenza.”[25] The European Commission uses the term
“novel flu virus.” WHO announced they would refer to the new
influenza virus as influenza A (H1N1) or “influenza A (H1N1) virus,
human”[26] as opposed to “swine flu,” also to avoid suggestions that
eating pork products carried a risk of infection.[27,28]
The outbreak has also been called the “H1N1 influenza,” “2009
H1N1 flu,” or “swine-origin influenza.” However, Seth Borenstein,
writing for the Associated Press quoted several experts who
objected to any name change at all [Figure 1].[29-33]
The hemagglutinin (HA) and neuraminidase (NA) proteins are
shown on the surface of the particle. The viral RNAs that make up
the genome are shown as red coils inside the particle and are bound
to ribonuclear proteins (RNPs). Influenza, commonly known as flu,
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
is an infectious disease of birds and mammals caused by an RNA
virus of the family Orthomyxoviridae (the influenza viruses) [Figure 2].
Classification
Of the three genera of influenza viruses that cause human flu, two
also cause influenza in pigs, with influenza virus A being common
in pigs and influenza virus C being rare.[39] Influenza virus B has
not been reported in pigs. Within influenza virus A and influenza
virus C, the strains found in pigs and humans are largely distinct,
although due to reassortment, there have been transfers of genes
among strains crossing swine, avian, and human species boundaries.
Influenza C
Influenza C viruses infect both humans and pigs, but do not infect
birds.[40] Transmission between pigs and humans have occurred in the
past.[41] For example, influenza C caused small outbreaks of a mild
form of influenza amongst children in Japan and California.[42] Due to
its limited host range and the lack of genetic diversity in influenza
C, this form of influenza does not cause pandemics in humans.[43]
Figure 1: Generation of pandemic influenza strain
Figure 2: Preliminary negative stained transmission electron micrograph
(TEM) depicted some the ultra structural morphology of the A/CA/4/09
swine flu virus.[36, 37,38]
111
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
Influenza A
Swine influenza is known to be caused by influenza A subtypes
H1N1,44 H1N2,[44] H3N1,[45] H3N2,[44] and H2N3.[46] In pigs, three
influenza A virus subtypes (H1N1, H3N2, and H1N2) are the most
common strains worldwide.[47] In the United States, the H1N1
subtype was exclusively prevalent among swine populations before
1998; however, since late August 1998, H3N2 subtypes have been
isolated from pigs. As of 2004, H3N2 virus isolates in US swine and
turkey stocks were triple reassortants, containing genes from human
(HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA)
lineages [Figure 3].[48]
Virus characteristics
The virus is a novel strain of influenza for which human populations
have been neither vaccinated nor naturally immunized.[49] It was
also determined that the strain contained genes from four different
flu viruses: North American swine influenza; North American avian
influenza; human influenza; and two swine influenza viruses typically
found in Asia and Europe. Further analysis showed that several of
the proteins of the virus are most similar to strains that cause mild
symptoms in humans, leading some to suggest that the virus is
unlikely to cause severe symptoms for most people.[50]
History
Swine influenza was first proposed to be a disease related to
human influenza during the 1918 flu pandemic, when pigs became
sick at the same time as humans.[51] The first identification of an
influenza virus as a cause of disease in pigs occurred about 10 years
later, in 1930. For the following 60 years, swine influenza strains
were almost exclusively H1N1. Then, between 1997 and 2002, new
strains of three different subtypes and five different genotypes
emerged as causes of influenza among pigs in North America. In
1997–1998, H3N2 strains emerged. These strains, which include
genes derived by reassortment from human, swine and avian viruses,
have become a major cause of swine influenza in North America.
Reassortment between H1N1 and H3N2 produced H1N2. In 1999
in Canada, a strain of H4N6 crossed the species barrier from birds
to pigs, but was contained on a single farm.[52]
The H1N1 form of swine flu is one of the descendants of the
strain that caused the 1918 flu pandemic.[53,54] As well as persisting
in pigs, the descendants of the 1918 virus have also circulated
in humans through the 20th century, contributing to the normal
seasonal epidemics of influenza.[54] However, direct transmission
from pigs to humans is rare, with only 12 cases in the United States
since 2005.[55] Nevertheless, the retention of influenza strains in pigs
after these strains have disappeared from the human population
might make pigs a reservoir where influenza viruses could persist,
later emerging to reinfect humans once human immunity to these
strains has waned.[56]
Swine flu has been reported numerous times as a zoonosis in
humans, usually with a limited distribution, rarely with a widespread
distribution. Outbreaks in swine are common and cause significant
economic losses in industry, primarily by causing stunting and
extended time to market. For example, this disease costs the British
meat industry about £65 million every year.[57]
Annual influenza epidemics are estimated to affect 5–15% of the
global population, resulting in severe illness in 3–5 million patients
and causing 250,000–500,000 deaths worldwide. In industrialized
countries, severe illness and deaths occur mainly in the high-risk
populations of infants, the elderly and chronically ill patients.[58]
In addition to these annual epidemics, the influenza A virus caused
three major global pandemics during the 20th century: the Spanish
flu in 1918, Asian flu in 1957, and Hong Kong flu in 1968–69. These
pandemics were caused by influenza A virus that had undergone
major genetic changes and for which the population did not possess
significant immunity.[58,59] The overall effects of these pandemics are
summarized in Table 1.
The influenza virus has also caused several pandemic threats
over the past century, including the pseudo-pandemic of 1947, the
1976 swine flu outbreak, and the 1977 Russian flu, all caused by the
H1N1 subtype.[59] The world has been at an increased level of alert
since the SARS epidemic in Southeast Asia (caused by the SARS
corona virus).[60] The level of preparedness was further increased and
sustained with the advent of the H5N1 bird flu outbreaks because
of H5N1’s high fatality rate, although the strains currently prevalent
have limited human-to-human transmission (anthroponotic)
capability, or epidemicity.[61,62]
People who contracted flu prior to 1957 may have some immunity.
A May 20, 2009, New York Times article stated: “Tests on blood serum
from older people showed that they had antibodies that attacked
the new virus, Dr. Daniel Jernigan, chief flu epidemiologist at the
Centers for Disease Control and Prevention, said in a telephone
news conference. That does not mean that everyone over 52 is
immune, since some Americans and Mexicans older than that have
died of the new flu.”[63]
1918 pandemic in humans
The 1918 flu pandemic in humans was associated with H1N1 and
influenza appearing in pigs;[54] this may reflect a zoonosis either
Table 1: Flu pandemics over last 100 years[61,64,65]
Figure 3: Structure of the influenza viron. (H1N1 Influenza virus)[35]
112
Pandemic
Year
Influenza
A virus
subtype
People
infected
(approx)
Deaths
(est.)
Case
fatality
rate %
Spanish flu
Asian flu
Hong
Kong flu
1918–19
1957
H1N1
H2N2
1 billion
---
50 million
2 million
>2.5
<0.1
1968–69
H3N2
---
1 million
<0.1
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
from swine to humans or from humans to swine. Although it is not
certain in which direction the virus was transferred, some evidence
suggests that, in this case, pigs caught the disease from humans.
For instance, swine influenza was only noted as a new disease of
pigs in 1918, after the first large outbreaks of influenza among
people.[51] Although a recent phylogenetic analysis of more recent
strains of influenza in humans, birds, and swine suggests that the
1918 outbreak in humans followed a reassortment event within a
mammal,[66] the exact origin of the 1918 strain remains elusive.[67]
1976 US outbreak
On February 5, 1976, in the United States an army recruit at Fort
Dix said he felt tired and weak. He died the next day and four of
his fellow soldiers were later hospitalized. Two weeks after his
death, health officials announced that the cause of death was a
new strain of swine flu. The strain, a variant of H1N1, is known as
A/New Jersey/1976 (H1N1). It was detected only from January 19 to
February 9 and did not spread beyond Fort Dix.[68] This new strain
appeared to be closely related to the strain involved in the 1918 flu
pandemic. Moreover, the ensuing increased surveillance uncovered
another strain in circulation in the United States: A/Victoria/75
(H3N2) spread simultaneously, also caused illness, and persisted
until March.[68] Alarmed public health officials decided action must
be taken to head off another major pandemic, and urged President
Gerald Ford that every person in the United States be vaccinated
for the disease.[69]
The vaccination program was plagued by delays and public
relations problems.[70] On October 1, 1976, the immunization
program began and by October 11, approximately 40 million
people, or about 24% of the population, had received swine flu
immunizations. That same day, three senior citizens died soon
after receiving their swine flu shots and there was a media outcry
linking the deaths to the immunizations, despite the lack of positive
proof. According to science writer Patrick Di Justo, however, by the
time the truth was known—that the deaths were not proven to be
related to the vaccine—it was too late. “The government had long
feared mass panic about swine flu—now they feared mass panic
about the swine flu vaccinations.” This became a strong setback
to the program.[71] There were reports of the Guillain–Barré (GBS)
syndrome, a paralyzing neuromuscular disorder, affecting some
people who had received swine flu immunizations. This syndrome
is a rare side effect of modern influenza vaccines, with an incidence
of about one case per million vaccinations.[72] As a result, Di Justo
writes that “the public refused to trust a government-operated
health program that killed old people and crippled young people.”
In total, less than 33% of the population had been immunized by
the end of 1976. The National Influenza Immunization Program
was effectively halted on December 16. Overall, there were about
500 cases of the GBS, resulting in death from severe pulmonary
complications for 25 people, which, according to Dr. P. Haber,
were probably caused by an immunopathological reaction to the
1976 vaccine. Other influenza vaccines have not been linked to
GBS, though caution is advised for certain individuals, particularly
those with a history of GBS.[73,74] Still, as observed by a participant
in the immunization program, the vaccine killed more Americans
than the disease did.[75]
1988 Zoonosis
In September 1988, a swine flu virus killed one woman and
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
infected others. —Thirty-two-year-old Barbara Ann Wieners was
8-month pregnant when she and her husband, Ed, became ill after
visiting the hog barn at a county fair in Walworth County, Wisconsin.
Barbara died 8 days later, after developing pneumonia.[76] The only
pathogen identified was an H1N1 strain of swine influenza virus.[77]
Doctors were able to induce labor and deliver a healthy daughter
before she died. Her husband recovered from his symptoms.
Influenza like illness (ILI) was reportedly widespread among the
pigs exhibited at the fair. A total of 76% of 25 swine exhibitors aged
9–19 tested positive for antibodies to SIV, but no serious illnesses
were detected among this group. Additional studies suggested
between one and three health care personnel who had contact with
the patient developed mild influenza-like illnesses with antibody
evidence of swine flu infection. However, there was no community
outbreak.[78,79]
1998 US outbreak in swine
In 1998, swine flu was found in pigs in four US states. Within
a year, it had spread through pig populations across the United
States. Scientists found that this virus had originated in pigs as
a recombinant form of flu strains from birds and humans. This
outbreak confirmed that pigs can serve as a crucible where novel
influenza viruses emerge as a result of the reassortment of genes
from different strains.[80-82]
2007 Philippine outbreak in swine
On August 20, 2007, Department of Agriculture officers
investigated the outbreak (epizootic) of swine flu in Nueva Ecija and
Central Luzon, Philippines. The mortality rate is less than 10% for
swine flu, unless there are complications like hog cholera. On July 27,
2007, the Philippine National Meat Inspection Service (NMIS) raised
a hog cholera “red alert” warning Metro Manila and five regions of
Luzon after the disease spread to backyard pig farms in Bulacan and
Pampanga, even if these tested negative for the swine flu virus.[83,84]
2009 Outbreak in humans
The 2009 flu outbreak is due to a new strain of subtype H1N1
not previously reported in pigs.[85] In late April, Margaret Chan,
WHO’s director-general, declared a “public health emergency of
international concern” under the rules of WHO’s new International
Health Regulations when the first cases of the H1N1 virus were
reported in the United States.[86,87] Following the outbreak, on May
2, 2009, it was reported in pigs at a farm in Alberta, Canada, with
a link to the outbreak in Mexico. The pigs were suspected to have
caught this new strain of virus from a farm worker who had recently
returned from Mexico, and then showed symptoms of an influenzalike illness.[88] These are probable cases, pending confirmation
by laboratory testing. The new strain was initially described as
an apparent reassortment of at least four strains of influenza A
virus subtype H1N1, including one strain endemic in humans, one
endemic in birds, and two endemic in swine.[8] Subsequent analysis
suggested that it was a reassortment of just two strains, both found
in swine.[7] Although initial reports identified the new strain as
swine influenza (i.e., a zoonosis originating in swine), its origin is
unknown. Several countries took precautionary measures to reduce
the chances for a global pandemic of the disease [Table 2].[89]
113
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
Transmission to humans
Table 2: Detected human cases by country[90-95]
Country
Mexico
United States
Canada
Costa Rica
Japan
United Kingdom
Spain
Chile
Panama
Australia
South Korea
Ecuador
Peru
Argentina
France
Italy
Kuwait
Germany
Colombia
Mainland China
Hong Kong
Brazil
New Zealand
Taiwan
Taiwan
Israel
Belgium
El Salvador
Other
Cases
Deaths
Laboratory
confirmed#
Probable
(Suspected) ‡
Confirmed
(Suspected)‡
12,954
13,791¤
4,806
6,764¤
921
33
361
184
136
119
76
66
29
28
27
19
19
19
18
17
16
13
10
9
9
9
9
7
6
N/A
N/A§
N/A§
N/A
N/A§
128 (120)
N/A
N/A (113)
0 (57)
0
0
1 (132)
0 (24)
0 (1)
0 (0)
0 (22)
0 (19)
N/A
N/A
N/A
1 (164)
N/A
0 (57)
17
10 (18)
1 (5)
N/A
N/A
0 (60)
92
102 (~100)
85 (~100)
14
2
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Number of countries with confirmed cases: 55, Number of countries with
confirmed or suspected cases: 60, #Some authorities have stopped testing all
but seriously ill patients,[91] so many cases will not be confirmed. On May 15,
2009, the CDC's Jan Jernigan estimated that there were "probably upwards
of maybe 100,000" cases in the United States.[92], §The governments of
Mexico[93] and Canada[94] have stopped reporting suspected cases, ‡Suspected
and probable cases have not been confirmed as being due to this strain of
influenza by laboratory tests, although some other strains may have been ruled
out, ¤The "confirmed cases" figure for the United States includes probable
cases, (y) Virus is known to have been transmitted in country, but no specific
numbers available.
Transmission
Transmission between pigs
Influenza is quite common in pigs, with about half of breeding pigs
having been exposed to the virus in the United States. Antibodies
to the virus are also common in pigs in other countries.[96] The main
route of transmission is through direct contact between infected and
uninfected animals.[47] These close contacts are particularly common
during animal transport. Intensive farming may also increase the
risk of transmission, as the pigs are raised in very close proximity
to each other.[97,98] The direct transfer of the virus probably occurs
either by pigs touching noses, or through dried mucus. Airborne
transmission through the aerosols produced by pigs coughing or
sneezing is also an important means of infection.[47] The virus usually
spreads quickly through a herd, infecting all the pigs within just
a few days.[5] Transmission may also occur through wild animals,
such as wild boar, which can spread the disease between farms.[99]
114
People who work with poultry and swine, especially people with
intense exposures, are at an increased risk of zoonotic infection
with influenza virus endemic in these animals, and constitute a
population of human hosts in which zoonosis and reassortment
can cooccur.[100] Vaccination of these workers against influenza
and surveillance for new influenza strains among this population
may therefore be an important public health measure.[101] The
transmission of influenza from swine to humans who work with
swine was documented in a small surveillance study performed in
2004 at the University of Iowa.[102] This study among others forms
the basis of a recommendation that people whose jobs involve
handling poultry and swine be the focus of increased public health
surveillance.[100] Other professions at particular risk of infection
are veterinarians and meat processing workers, although the risk
of infection for both of these groups is lower than that of farm
workers.[103]
Interaction with avian H5N1 in pigs
Pigs are unusual as they can be infected with influenza strains
that usually infect three different species: pigs, birds, and humans.
This makes pigs a host where influenza viruses might exchange
genes, producing new and dangerous strains.[104] Avian influenza
virus H3N2 is endemic in pigs in China and has been detected in
pigs in Vietnam, increasing fears of the emergence of new variant
strains.[105] H3N2 evolved from H2N2 by an antigenic shift.[106] In
August 2004, researchers in China found H5N1 in pigs.[107]
These H5N1 infections may be quite common in a survey of 10
apparently healthy pigs housed near poultry farms in West Java,
where avian flu had broken out, and 5 of the pig samples contained
the H5N1 virus. The Indonesian government has since then found
similar results in the same region. Additional tests of 150 pigs
outside the area were negative.[108,109]
Factors of transmitting swine flu
Sneezing and coughing
There are little data available on the risk of airborne transmission
of this particular virus. Mexican authorities have distributed surgical
masks to the general public. The UK Health Protection Agency
considers facial masks unnecessary for the general public.[110] Many
authorities recommend the use of respirators by health care workers
in the vicinity of pandemic flu patients, particularly during aerosol
generating procedures (e.g., intubations, chest physiotherapy,
bronchoscopy).
Touching
Infection can be caused by touching something with flu viruses
on it and then touching your mouth or nose. The virus can have a
lifetime of up to 2 h outside the body, and thus can be transmitted by
handling door knobs, glasses, kitchen utensils, or touching the skin
of an infected person and then touching your own mouth or eyes.
Pork consumption
The leading international health agencies have stressed that the
“influenza viruses are not known to be transmissible to people
through eating processed pork or other food products derived
from pigs.”[111]
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
Signs and symptoms
The signs of infection with swine flu are similar to influenza,
and include a fever, coughing, headaches, pain in the muscles or
joints, sore throat, chills, fatigue, and runny nose. Diarrhea and
vomiting have also been reported in some cases.[112,113] People at a
higher risk of serious complications include people age 65 years
and older, children younger than 5 years of age, pregnant women,
people of any age with chronic medical conditions (such as asthma,
diabetes, or heart disease), and people who are immunosuppressed
(e.g., taking immunosuppressive medications or infected with HIV).
In children, certain symptoms may require emergency medical
attention, including blue lips and skin, dehydration, rapid breathing,
excessive sleeping, and significant irritability that includes a lack of
desire to be held. In adults, shortness of breath, pain in the chest
or abdomen, sudden dizziness or confusion may indicate the need
for emergency care. In both children and adults, persistent vomiting
or the return of flu-like symptoms that include a fever and cough
may require medical attention.[112]
There is mounting evidence that the symptoms are so far milder
than health officials feared. As of May 21, 2009, for instance,
despite 201 confirmed cases in New York City, most have been mild
and there has been only one confirmed death from the virus.[114]
Similarly, Japan has reported 279, mostly mild flu cases, and no
deaths,[115] with their government now reopening schools, stating
that the “virus should be considered more like a seasonal flu.”[116] In
Mexico, where the outbreak began last month, Mexico City officials
have lowered their swine flu alert level as no new cases have been
reported for a week.[117]
these six people, one was pregnant, one had leukemia, one had
Hodgkin’s disease and two were known to be previously healthy.
Despite these apparently low numbers of infections, the true rate
of infection may be higher, since most cases only cause a very mild
disease, and will probably never be reported or diagnosed.[119]
According to CDC, in humans the symptoms of the 2009 “swine
flu” H1N1 virus are similar to those of influenza and of influenzalike illness in general. Symptoms include fever, cough, sore throat,
body aches, headache, chills, and fatigue. The 2009 outbreak has
shown an increased percentage of patients reporting diarrhea and
vomiting. The 2009 H1N1 virus is not zoonotic swine flu, as it is not
transmitted from pigs to humans, but from person to person.[120]
Because these symptoms are not specific to swine flu, a differential
diagnosis of probable swine flu requires not only symptoms but
also a high likelihood of swine flu due to the person’s recent
history. For example, during the 2009 swine flu outbreak in the
United States, CDC advised physicians to “consider swine influenza
infection in the differential diagnosis of patients with acute febrile
respiratory illness who have either been in contact with persons
with confirmed swine flu, or who were in one of the five US states
that have reported swine flu cases or in Mexico during the 7 days
preceding their illness onset.” A diagnosis of confirmed swine flu
requires laboratory testing of a respiratory sample (a simple nose
and throat swab) [Figure 5].[121]
Mutation potential
Direct transmission of a swine flu virus from pigs to humans is
occasionally possible (called zoonotic swine flu). In all, 50 cases
are known to have occurred since the first report in the medical
literature in 1958, which have resulted in a total of 6 deaths. Of
On May 22, 2009, WHO chief Dr. Margaret Chan said that the virus
must be closely monitored in the southern hemisphere, as it could
mix with ordinary seasonal influenza and change in unpredictable
ways. “In cases where the H1N1 virus is widespread and circulating
within the general community, countries must expect to see more
cases of severe and fatal infections,” she said. “This is a subtle,
sneaky virus.”
An international team of researchers who analyzed all eight
genes of the new virus confirmed its sneakiness, saying it “was so
different from its ancestral strains that it must have been circulating
undetected for years.” They confirmed that it is a hybrid of two other
mixtures—one a so-called triple reassortant of pig, bird, and human
viruses, and another group of swine viruses from Europe and Asia.[122]
This has led other experts to become concerned that the new
virus strain could mutate over the coming months. Guan Yi, a
Figure 4: Main symptoms of Swine flu in Pigs[5]
Figure 5: Main symptoms of swine flu in humans[118]
In swine
In pigs, influenza infection produces fever, lethargy, sneezing,
coughing, difficulty in breathing, and decreased appetite. In some
cases, the infection can cause abortion. Although mortality is usually
low (around 1–4%),[5] the virus can produce weight loss and poor
growth, causing economic loss to farmers. Infected pigs can lose up
to 12 pounds of body weight over a 3- to 4-week period [Figure 4].[47]
In humans
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
115
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
leading virologist from the University of Hong Kong, for instance,
has described the new H1N1 influenza virus as “very unstable,”
meaning it could mix and swap genetic material when exposed to
other viruses. During an interview, he said “Both H1N1 and H5N1
are unstable so the chances of them exchanging genetic material
are higher, whereas a stable (seasonal flu) virus is less likely to take
on genetic material.” The H5N1 virus is mostly limited to birds,
but in rare cases when it infects humans it has a mortality rate of
60–70%. Experts therefore worry about the emergence of a hybrid
of the more dangerous H5N1 with the more transmissible H1N1,
especially since H5N1 is now believed to be endemic in countries
like China, Indonesia, Vietnam, and Egypt.[123] The virulence of avian
flu is in part due to a nonstructural protein, NS1, which is distinct
from its surface antigens and so could potentially be introduced
into other flu virus subtypes (subtypes are defined according to
their surface antigens—the H and N numbers).[124]
Pandemic potential
The WHO and CDC officials remain concerned that this outbreak
may yet become a pandemic. WHO declared a pandemic alert
level of 5, out of a maximum 6, which describes the degree to
which the virus has been able to spread among humans, and uses
a pandemic severity index, which predicts the number of fatalities
if 30% of the human population were infected. By the end of April,
however, some scientists believed that this strain was unlikely to
cause as many fatalities as earlier pandemics, and may not even
be as damaging as a typical flu season.[126] WHO Director General
Margaret Chan, on May 22, continued to stop short of declaring
the outbreak a “pandemic,” by moving to alert level 6, because of
recent doubts fostered by its mild symptoms to date[58] along with
fear that a pandemic “declaration would trigger mass panic” and
be economically and politically damaging to many countries.[127]
According to some experts, however, the current outbreak is
already a pandemic. Michael Osterholm, director of the Center
for Infectious Disease Research and Policy of the University of
Minneapolis, feels that WHO’s criteria for a pandemic have been met.
While Britain’s Health Secretary Alan Johnson has requested that the
disease’s severity and other determinants, besides its geographic
spread, need to be considered before the pandemic alert is raised to
the highest of WHO’s 6-level scale, since a move to phase 6 means
that “emergency plans are instantly triggered around the globe.”
In addition, at phase 6, many pharmaceutical companies would
switch from making seasonal flu shots to pandemic-specific vaccine,
“potentially creating shortages of an immunization to counter the
normal winter flu season.” Keiji Fukuda, WHO’s assistant director
general of Health Security and Environment, states that a move to
phase 6 would “signify a really substantial increase in risk of harm
to people.”
Osterholm feels that the primary concern should be “scientific
integrity,” stating, “If they want to change the definition, then go
ahead. But don’t say that we are not in phase 6 right now because
we don’t want to go there.” Rather than redefining what constitutes
a pandemic, he suggests that health officials should help people
understand that the current threat may resemble the 1957 or 1968
pandemics, in which fewer than 4 million people died, rather than
the 1918 Spanish flu, blamed for killing about 50 million [Table 3].[128]
Prevention
Prevention of swine influenza has three components: prevention
in swine, prevention of transmission to humans and prevention of
its spread among humans.
Prevention in swine
Methods of preventing the spread of influenza among swine
include facility management, herd management, and vaccination.
Because much of the illness and death associated with swine flu
involves secondary infection by other pathogens, control strategies
that rely on vaccination may be insufficient.
Control of swine influenza by vaccination has become more
difficult in recent decades, as the evolution of the virus has
resulted in inconsistent responses to traditional vaccines. Standard
commercial swine flu vaccines are effective in controlling the
infection when the virus strains match enough to have significant
cross-protection, and custom (autogenous) vaccines made from
the specific viruses isolated are created and used in the more
difficult cases.[129,130] Present vaccination strategies for SIV control
and prevention in swine farms typically include the use of one of
several bivalent SIV vaccines commercially available in the United
States. Of the 97 recent H3N2 isolates examined, only 41 isolates
had strong serologic cross-reactions with antiserum to three
commercial SIV vaccines. Since the protective ability of influenza
vaccines depends primarily on the closeness of the match between
the vaccine virus and the epidemic virus, the presence of nonreactive
H3N2 SIV variants suggests that current commercial vaccines
might not effectively protect pigs from infection with a majority of
H3N2 viruses.[131,132] The United States Department of Agriculture
Table 3: WHO pandemic influenza phases (2009)[125]
Phase
Description
Phase 1
No animal influenza virus circulating among animals have been reported to cause infection in humans.
An animal influenza virus circulating in domesticated or wild animals is known to have caused infection in humans and is
therefore considered a specific potential pandemic threat.
An animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has
not resulted in human-to-human transmission sufficient to sustain community-level outbreaks.
Human to human transmission of an animal or human-animal influenza reassortant virus able to sustain community-level
outbreaks has been verified.
The same identified virus has caused sustained community level outbreaks in two or more countries in one WHO region.
In addition to the criteria defined in Phase 5, the same virus has caused sustained community level outbreaks in at least one
other country in another WHO region.
Levels of pandemic influenza in most countries with adequate surveillance have dropped below peak levels.
Levels of influenza activity have returned to the levels seen for seasonal influenza in most countries with adequate surveillance.
Phase 2
Phase 3
Phase 4
Phase 5
Phase 6
Post peak period
Post pandemic period
116
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
researchers say that while pig vaccination keeps pigs from getting
sick, it does not block infection or shedding of the virus.[133]
Facility management includes using disinfectants and ambient
temperature to control virus in the environment. The virus is unlikely
to survive outside living cells for more than 2 weeks, except under
cold (but above freezing) conditions and it is readily inactivated by
disinfectants.[5] Herd management includes not adding pigs carrying
influenza to herds that have not been exposed to the virus. The
virus survives in healthy carrier pigs for up to 3 months and can be
recovered from them between outbreaks. Carrier pigs are usually
responsible for the introduction of SIV into previously uninfected
herds and countries, so new animals should be quarantined.[96] After
an outbreak, as immunity in exposed pigs wanes, new outbreaks of
the same strain can occur.[5]
Prevention in humans
Swine can be infected by both avian and human influenza strains
of influenza, and therefore are hosts where the antigenic shifts can
occur that create new influenza strains.
The transmission from swine to humans is believed to occur mainly
in swine farms where farmers are in close contact with live pigs.
Although strains of swine influenza are usually not able to infect
humans, this may occasionally happen, so farmers and veterinarians
are encouraged to use a face mask when dealing with infected
animals. The use of vaccines on swine to prevent their infection
is a major method of limiting swine-to-human transmission. Risk
factors that may contribute to swine-to-human transmission include
smoking and not wearing gloves when working with sick animals.[134]
Prevention of human-to-human transmission
Influenza spreads between humans through coughing or sneezing
and people touching something with the virus on it and then
touching their own nose or mouth.[135] Swine flu cannot be spread
by pork products, since the virus is not transmitted through food.[73]
The swine flu in humans is most contagious during the first 5 days
of the illness although some people, most commonly children, can
remain contagious for up to 10 days. Diagnosis can be made by
sending a specimen, collected during the first 5 days for analysis.[136]
Recommendations to prevent spread of the virus among humans
include using standard infection control against influenza. This
includes frequent washing of hands with soap and water or with
alcohol-based hand sanitizers, especially after being out in public.[137]
Chances of transmission are also reduced by disinfecting household
surfaces, which can be done effectively with a diluted chlorine bleach
solution.[138] Although the current trivalent influenza vaccine is
unlikely to provide protection against the new 2009 H1N1 strain,[139]
vaccines against the new strain are being developed and could be
ready as early as June 2009.[140]
Experts agree that hand-washing can help prevent viral infections,
including ordinary influenza and the swine flu virus. Influenza can
spread in coughs or sneezes, but an increasing body of evidence
shows that small droplets containing the virus can linger on
tabletops, telephones, and other surfaces and be transferred via the
fingers to the mouth, nose, or eyes. Alcohol-based gel or foam hand
sanitizers work well to destroy viruses and bacteria. Anyone with
flu-like symptoms such as a sudden fever, cough, or muscle aches
should stay away from work or public transportation and should
contact a doctor to be tested. Social distancing is another tactic. It
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
means staying away from other people who might be infected and
can include avoiding large gatherings, spreading out a little at work,
or perhaps staying home and lying low if an infection is spreading in
a community. Public health and other responsible authorities have
action plans which may request or require social distancing actions
depending on the severity of the outbreak.
Treatment
Treatments for influenza include a range of medications and
therapies that are used in response to influenza. Treatments may
either directly target the influenza virus itself, or instead they may
just offer relief to symptoms of the disease, while the body’s own
immune system works to recover from infection. The two main
classes of antiviral drugs used against influenza are neuraminidase
inhibitors, such as zanamivir and oseltamivir, or inhibitors of the viral
M2 protein, such as amantadine and rimantadine. These drugs can
reduce the severity of symptoms if taken soon after infection and can
also be taken to decrease the risk of infection. However, viral stains
have emerged that show drug resistance to both classes of drug.
In swine
As swine influenza is rarely fatal to pigs, little treatment beyond
rest and supportive care is required.[96] Instead veterinary efforts
are focused on preventing the spread of the virus throughout the
farm, or to other farms.[47] Vaccination and animal management
techniques are most important in these efforts. Antibiotics are also
used to treat this disease, which although have no effect against
the influenza virus, do help prevent bacterial pneumonia and other
secondary infections in influenza-weakened herds.[96]
In humans
If a person becomes sick with swine flu, antiviral drugs can make
the illness milder and make the patient feel better faster. They
may also prevent serious flu complications. For treatment, antiviral
drugs work best if started soon after getting sick (within 2 days of
symptoms). Besides antivirals, palliative care, at home or in hospital,
focuses on controlling fevers and maintaining fluid balance. The US
Centers for Disease Control and Prevention recommends the use of
Tamiflu (oseltamivir) or Relenza (zanamivir) for the treatment and/
or prevention of infection with swine influenza viruses; however,
the majority of people infected with the virus make a full recovery
without requiring medical attention or antiviral drugs.[141] The
virus isolates in the 2009 outbreak have been found resistant to
amantadine and rimantadine.[142]
In the United States, on April 27, 2009, the FDA issued Emergency
Use Authorizations (EUAs) to make available Relenza and Tamiflu
antiviral drugs to treat the swine influenza virus in cases for which
they are currently unapproved. The agency issued these EUAs to
allow treatment of patients younger than the current approval allows
and to allow the widespread distribution of the drugs, including
distribution by nonlicensed volunteers.[143]
Personal hygiene
Recommendations to prevent infection by the virus consist of
the standard personal precautions against influenza. This includes
117
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
frequent washing of hands with soap and water or with alcoholbased hand sanitizers, especially after being out in public. The
CDC advises not touching the mouth, nose, or eyes, as these are
primary modes of transmission. When coughing, they recommend
coughing into a tissue and disposing of the tissue, then immediately
washing the hands.[144] Chances of transmission are also reduced by
disinfecting household surfaces, which can be done effectively with
a diluted chlorine bleach solution.[145]
Symptomatic treatment
The US authority on disease prevention, the Centers for Disease
Control and Prevention, recommends that persons suffering from
influenza infections
• Stay at home
• Get plenty of rest
• Drink a lot of liquids
• Do not smoke or drink alcohol
• Consider over-the-counter medications to relieve flu symptoms
• Consult a doctor early on for best possible treatment
• Remain alert for emergency warning signs.
Warning signs are symptoms that indicate that the disease is
becoming serious and needs immediate medical attention. These
include
• Difficulty in breathing or shortness of breath
• Pain or pressure in the chest or abdomen
• Dizziness
• Confusion
• Severe or persistent vomiting.
In children, other warning signs include irritability, failing to wake
up and interact, rapid breathing, and a bluish skin color. Another
warning sign in children is the flu symptoms appear to resolve, but
then reappear with fever and a bad cough.[159,160]
Antiviral drugs
According to the CDC, antiviral drugs can be given to treat
those who become severely ill; however, these antiviral drugs are
prescription medicines (pills, liquid, or an inhaler) and act against
influenza viruses, including the H1N1 flu virus. There are two
influenza antiviral medications that are recommended for use
against the H1N1 flu. The drugs that are used for treating the H1N1
flu are called “oseltamivir” (Tamiflu) and “zanamivir” (Relenza). The
CDC notes that as the H1N1 flu spreads, these antiviral drugs may
become short in supply. Therefore, the drugs will be given first
to those people who have been hospitalized or are at a high risk
of complications. The drugs work best if given within 2 days of
becoming ill, but may be given later if illness is severe or used for
those at a high risk for complications.
When buying these medications, some agencies such as the
“MHRA” in the UK have recommended not using online sources, as
the WHO estimates that half the drugs sold by online pharmacies
without a physical address are counterfeit.[146] Medical experts
are also concerned that people “racing to grab up antiviral drugs
just to feel safe” may eventually lead to the virus developing drug
resistance. Partly as a result, experts suggest the medications should
be reserved for only the very ill or people with severe immune
deficiencies.[147]
In H3N2 strains, Tamiflu treatment leads to resistance in 0.4% of
adult cases and 5.5% of children. Resistant strains are usually less
transmissible; nonetheless, resistant human H1N1 viruses became
widely established in previous flu seasons. Marie-Paule Kiely, WHO
vaccine research director, has said that it is “almost a given” that
the new strain would undergo reassortment with resistant seasonal
flu viruses and acquire resistance, but it is not yet known at what
level resistance will appear.[148] Simulations suggest that if physicians
choose a second effective antiviral such as zanamivir (Relenza) as
first-line treatment in even a few percent of cases, this can greatly
delay the spread of resistant strains. Even a drug such as amantadine
(Symmetrel) for which resistance frequently emerges may be useful
in combination therapy.[149,150]
Antiviral treatment for novel (H1N1) influenza[151]
For antiviral treatment of novel influenza (H1N1) virus infection,
either oseltamivir or zanamivir is recommended [Table 4].
Recommendations for the use of antivirals may change as data on
antiviral effectiveness, clinical spectrum of illness, adverse events
from antiviral use, and antiviral susceptibility become available.
Clinical judgment is an important factor in treatment decisions.
Persons with suspected novel H1N1 influenza who present with
an uncomplicated febrile illness typically do not require treatment
unless they are at a higher risk for influenza complications, and in
areas with limited antiviral mediation availability, local public health
authorities might provide additional guidance about prioritizing
treatment within groups at a higher risk for infection.
Treatment is recommended for:
1. All hospitalized patients with confirmed, probable, or suspected
novel influenza (H1N1).
2. Patients who are at a higher risk for seasonal influenza
complications.
If a patient is not in a high-risk group or is not hospitalized, health
care providers should use clinical judgment to guide treatment
Table 4: Antiviral medication dosing recommendations for treatment or chemoprophylaxis of novel influenza A (H1N1)
infection.[158]
Agent, group
Adults
Children ≥ 12 months
Adults
Children 8
118
Treatment
15 kg or less
15-23 kg
24-40 kg
>40 kg
Chemoprophylaxis
Oseltamivir
75-mg capsule twice per day for 5 days
60 mg per day divided into 2 doses
90 mg per day divided into 2 doses
120 mg per day divided into 2 doses
150 mg per day divided into 2 doses
Zanamivir
Two 5-mg inhalations (10 mg total) twice per day
Two 5-mg inhalations (10 mg total) twice per day
(age, 7 years or older)
75-mg capsule once per day
30 mg once per day
45 mg once per day
60 mg once per day
75 mg once per day
Two 5-mg inhalations (10 mg total) once per day
Two 5-mg inhalations (10 mg total) once per day
(age, 5 years or older)
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
decisions, and when evaluating children should be aware that
the risk for severe complications from seasonal influenza among
children younger than 5 years of age is highest among children
younger than 2 years of age. Many patients who have had novel
influenza (H1N1) virus infection, but who are not in a high-risk
group have had a self-limited respiratory illness similar to typical
seasonal influenza. For most of these patients, the benefits of
using antivirals may be modest. Therefore, testing, treatment, and
chemoprophylaxis efforts should be directed primarily at persons
who are hospitalized or at a higher risk for influenza complications.
Once the decision to administer antiviral treatment is made,
treatment with zanamivir or oseltamivir should be initiated as soon
as possible after the onset of symptoms. Evidence for benefits from
antiviral treatment in studies of seasonal influenza is strongest
when treatment is started within 48 h of illness onset. However,
some studies of oseltamivir treatment of hospitalized patients with
seasonal influenza have indicated benefit, including reductions in
mortality or duration of hospitalization even for patients whose
treatment was started more than 48 h after the illness onset.
Recommended duration of treatment is 5 days. Antiviral doses
recommended for the treatment of novel H1N1 influenza virus
infection in adults or children 1 year of age or older are the same
as those recommended for seasonal influenza [Table 5]. Oseltamivir
use for children younger than 1 year of age was recently approved
by the US Food and Drug Administration (FDA) under an EUA, and
dosing for these children is age based [Table 6].
Antiviral chemoprophylaxis for novel (H1N1) influenza[152]
For antiviral chemoprophylaxis of novel (H1N1) influenza
virus infection, either oseltamivir or zanamivir is recommended
[Table 5]. The duration of antiviral chemoprophylaxis postexposure is
10 days after the last known exposure to novel (H1N1) influenza. The
indication for postexposure chemoprophylaxis is based upon close
contact with a person who is a confirmed, probable, or suspected
case of novel influenza A (H1N1) virus infection during the infectious
period of the case. The infectious period for persons infected
with the novel influenza A (H1N1) virus is assumed to be similar
to that observed in studies of seasonal influenza. With seasonal
influenza, studies have shown that people may be able to transmit
infection beginning 1 day before they develop symptoms to up to
Table 5: Dosing recommendations for antiviral treatment
of children younger than 1 year using oseltamivir
Age
Recommended treatment dose for 5 days
<3 months
3-5 months
6-11 months
12 mg twice daily
20 mg twice daily
25 mg twice daily
Table 6: Dosing recommendations for antiviral
chemoprophylaxis of children younger than 1 year using
oseltamivir
Age
Recommended prophylaxis dose for 10 days
<3 months
Not recommended unless situation judged
critical due to limited data on use in this age group
20 mg once daily
25 mg once daily
3-5 months
6-11 months
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
7 days after they get sick. Children, especially younger children,
might potentially be infectious for longer periods. However, for
this guidance, the infectious period is defined as 1 day before until 7
days after the case’s onset of illness. If the contact occurred with a
case whose illness started more than 7 days before contact with the
person under consideration for antivirals, then chemoprophylaxis
is not necessary. For pre-exposure chemoprophylaxis, antiviral
medications should be given during the potential exposure period
and continued for 10 days after the last known exposure to a
person with novel (H1N1) influenza virus infection during the case’s
infectious period. Oseltamivir can also be used for chemoprophylaxis
under the EUA for children less than 1 year of age.
Postexposure antiviral chemoprophylaxis with either oseltamivir
or zanamivir can be considered for the following:
1. Close contacts of cases (confirmed, probable, or suspected)
who are at a high risk for complications of influenza.
2. Health care personnel, public health workers, or first responders
who have had a recognized, unprotected close contact exposure
to a person with novel (H1N1) influenza virus infection
(confirmed, probable, or suspected) during that person’s
infectious period.
Pre-exposure antiviral chemoprophylaxis should only be used in
limited circumstances, and in consultation with local medical or
public health authorities. Certain persons at an ongoing occupational
risk for exposure who are also at a higher risk for complications
of influenza (e.g., health care personnel, public health workers, or
first responders who are working in communities with influenza A
H1N1 outbreaks) should carefully follow guidelines for appropriate
personal protective equipment or consider temporary reassignment.
Antiviral use for the control of novel H1N1 influenza
outbreaks[153-155]
The use of antiviral drugs for the treatment and chemoprophylaxis
of influenza has been a cornerstone for the control of seasonal
influenza outbreaks in nursing homes and other long-term care
facilities. At this time, no outbreaks of novel influenza A (H1N1) have
been reported in such settings. However, if such outbreaks were to
occur, it is recommended that ill patients be treated with oseltamivir
or zanamivir and that chemoprophylaxis with either oseltamivir
or zanamivir be started as early as possible to reduce the spread
of the virus as is recommended for seasonal influenza outbreaks
in such settings. Chemoprophylaxis should be administered
to all nonill residents and should continue for a minimum of 2
weeks. If surveillance indicates that new cases continue to occur,
chemoprophylaxis should be continued until approximately 7 days
after the illness onset in the last patient. In addition to antiviral
medications, other outbreak-control measures include appropriate
infection control, establishing cohorts of patients with confirmed
or suspected influenza, restricting staff movement between wards
or buildings, and restricting contact between ill staff or visitors and
patients, and active surveillance for new cases. Medical directors of
long-term care facilities should review their plans for the outbreak
control of influenza. In addition to use in nursing homes, antiviral
chemoprophylaxis also can be considered for controlling influenza
outbreaks in other closed or semiclosed settings (e.g., correctional
facilities, or other settings in which persons live in close proximity).
Children under 1 year of age
Children under 1 year of age are at a high risk for complications
119
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
from seasonal human influenza virus infection. The characteristics
of human infection novel (H1N1) influenza virus are still being
studied, and it is not known whether infants are at a higher risk for
complications associated with novel (H1N1) influenza virus infection
compared to older children and adults. Oseltamivir is not licensed for
use in children less than 1 year of age. However, limited safety data
on oseltamivir treatment for seasonal influenza in children less than
1 year of age suggest that severe adverse events are rare [Table 7].[156]
Vaccines
The purpose of a vaccine is to prime the body’s immune system
so that it is able to respond rapidly if it is later exposed to that
particular disease. The immune system fights viral diseases such as
flu by recognizing proteins (antigens) on or in the virus. A flu vaccine
contains either a safe version of the virus, or copies of its proteins.
It causes the immune cells that recognize these proteins to replicate
so that they are primed to respond to a later attack by this virus.
The vaccine does not itself cause flu, as it does not contain a virus
which could replicate within the body—if a whole virus is used, it
is killed before the vaccine is created. Using a whole virus, rather
than just isolated proteins, typically leads to a stronger immune
response. It can also lead to “cross-protection”—protection against
strains of a virus whose proteins differ slightly. This is useful if the
virus infecting the population undergoes a mutation, in which its
structure changes. For these reasons, vaccines made from isolated
proteins may also contain an adjuvant—a chemical designed to
enhance the immune system’s response to the viral protein, and to
maximize cross-protection.[157]
Development of an H1N1 vaccine
A vaccine against the newly emerging strain of H1N1 could stop
or slow its spread, and thus reduce its impact on health services,
workplaces, schools, and the economy. Since this virus differs
markedly from previous strains of H1N1, existing flu vaccines will not
work against it and a new vaccine needs to be developed. Several
different companies have the technology necessary to develop such
a vaccine. This involves making a preparation of the flu virus that
will cause an immune response without leading to symptoms of the
disease. This is done either by using killed flu viruses, or by using
proteins isolated from the virus. Vaccine development begins with
a sample of the virus responsible for the disease outbreak. Samples
of the H1N1 virus have been received by the Health Protection
Agency’s National Institute of Biological Standards and Control
(NIBSC), which is developing a strain of the virus suitable for use
in vaccine development with the aim of passing it onto vaccine
manufacturers.[157]
Table 7: OTC medicines provide relief for 'flu symptoms[161]
Symptom(s)
OTC Medicine
Fever, aches, pains, sinus pressure, sore throat
Nasal congestion, sinus pressure
Sinus pressure, runny nose, watery eyes, cough
Cough
Sore throat
Analgesics
Decongestants
Antihistamines
Cough suppressant
Local anesthetics
120
Conclusion
A new H1N1 influenza A virus has been identified in Mexico, and
has spread rapidly to other regions around the world. The World
Health Organization in collaboration with many other national and
international agencies is working efficiently to evaluate, diagnose,
and implement measures to contain the spread of this virus. Among
the many efforts is the timely release of the genomic sequences
from different viral isolates. The preliminary analyses show that
the closest relatives to this new strain are found in swine, and
occasionally in turkeys. Six segments of the virus are related to
swine viruses from North America and the other two (NA and M) to
swine viruses isolated in Europe/Asia. The closest clusters (for the HA
segment) in the NCBI data base are North America swine influenza
A (H1N2) and H3N2s. The closest relatives of the neuraminidase
(NA) gene of the new virus are influenza A isolates from 1992. As
more data become accessible, the evolution of this gene could be
clarified. Swine flu is a respiratory disease and has some elements of
a virus found in pigs. There is no evidence of this disease circulating
in pigs; scientists are investigating its origins. Swine flu has been
confirmed in a number of countries and it is spreading from human
to human, which could lead to what is referred to as a pandemic
flu outbreak. Flu viruses change over time. It is difficult to say if
the current outbreak will suddenly stop, or will continue. Health
officials continue to monitor the situation. Plans for pandemic and
emergency responses are ready for use. Pandemic flu is different
from ordinary flu because it’s a new flu virus that appears in humans
and spreads very quickly from person to person worldwide. WHO
is closely monitoring cases of swine flu globally to see whether
this virus develops into a pandemic. Because it’s a new virus,
no one will have immunity to it and everyone could be at risk of
catching it. This includes healthy adults as well as older people,
young children, and those with existing medical conditions. Flu
viruses are made up of tiny particles that can be spread through the
droplets that come out of your nose and mouth when you cough
or sneeze. When you cough or sneeze without covering your nose
and mouth with a tissue, those droplets can spread and others will
be at risk of breathing them in. If you cough or sneeze into your
hand, those droplets and the germs in them are then easily spread
from your hand to any hard surfaces that you touch, and they can
live on those surfaces for some time. Everyday items such as door
handles, computer keyboards, mobile and ordinary phones, and
the TV remote control are all common surfaces where flu viruses
can be found. If other people touch these surfaces and then touch
their faces, the germs can enter their systems and they can become
infected. That’s how all cold and flu viruses, including swine flu,
are passed on from person to person. The best thing you can do to
protect yourself is to follow good hygiene practices. These will help
to slow the spread of the virus and will be the single most effective
thing you can do to protect yourself and others from infection.
According to the Centre for Disease control and Prevention, the fact
that the flu’s infection activity is now monitored more closely may
help explain why more flu cases than normal are being recorded
in Mexico, the United States, and other countries. About half of
all influenza viruses being detected so far are the new H1N1 virus,
which experts acknowledge is no worse than seasonal influenza
for now. Human cases of a new form of influenza virus have been
identified in the United States, Mexico, Canada, Spain, Israel, UK,
and New Zealand. The majority of cases outside Mexico are still
being reported as a mild illness only. The pandemic alert level has
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
been raised by the World Health Organization if you have a flu-like
illness (fever and cough and fatigue) and have traveled to Mexico,
USA, or Canada in past few days. Current information suggests
antiviral drugs (Tamiflu and Relenza) are useful against these swine
influenza viruses. These drugs are available through pharmacists
and can be prescribed by GPs. Among all countries, Australia has
very good communicable disease surveillance and control systems
in place to detect and respond to outbreaks of illness. The World
Health Organization has declared this to be a public heath health
emergency of international concern.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Geering WA, Forman AJ, Nunn MJ. Exotic Diseases of Animals. Aust
Gov Publi Serv, Canberra, Australia; 1995. p. 242-5.
Easterday BC, Van Reeyh K. Swine Influenza. In: Diseases of Swine,
Ames, Iowa. USA: Iowa state University Press; 1999. p. 277-90.
Brown JH, Alexander DJ. Swine Vesicular Disease In: Zoonoses SR
Palmer, Lord Soulsey, Simpson DIH, editors. Oxford University Press.
Avon: Bath Press; 1998. p. 365-86.
Office International des Epizooties, 2002.
Swine Influenza. In: Merck Veterinary Manual. 8th ed. Philadelphia:
National Publishing Inc; 1998. p. 1106-7.
Swine Influenza. In: Veterinary Medicine. 8th ed. London: Saunders;
1997. p. 1045-7.
Trifonov V, Khiabanian H, Greenbaum B, Rabadan R. The origin of the
recent swine influenza A(H1N1) virus infecting humans. Euro Surveill
2009;14:19193.
http://www.eurosurveillance.org/images/dynamic/EE/V14N17/art19193.
pdf.
Deadly new flu virus in U.S. and Mexico may go pandemic. New
Scientist. Archived from the original on April 28, 2009. http://www.
webcitation.org/5gNd9HTT9. [Last cited on 2009 April 28].
Myers KP, Olsen CW, Setterquist SF, Capuano AW, Donham KJ, Thacker
EL, et al. Are swine workers in the United States at increased risk of
infection with zoonotic influenza virus? Clin Infect Dis 2006;42:14-20.
Webby RJ, Rossow K, Erickson G, Sims Y, Webster R. Multiple lineages
of antigenically and genetically diverse influenza A virus co-circulate
in the United States swine population. Virus Res 2004;103:67-73.
Influenza: Pigs, People and Public Health National Pork Board 2004;2:
1-4.
Olsen CW, Brammer L, Easterday BC, Arden N, Belay E, Baker I, et al.
Serologic evidence of H1 swine Influenza virus infection in swine farm
residents and employees. Emerg Infect Dis 2002;8:814-9.
Ayora-Talavera G, Cadavieco-Burgos JM, Canul-Armas AB. Serologic
evidence of human and swine influenza in Mayan persons. Emerg
Infect Dis 2005;11:158-60.
Swine influenza: a zoonosis Veterinary Sciences Tomorrow, 2003.
Brown IH. The epidemiology and evolution of influenza viruses in pigs.
Vet Microbiol 2000;74:29-46.
WHO Manual on Animal Influenza Diagnosis and Surveillance, 2004.
Fact sheet Pandemic Preparedness awareness instructor manual Toucan
Ed Inc, 2007.
Martin A, Krauss C. Pork industry fights concerns over swine flu. The
New York Times, 2009.
Gillam Carey. US farmers fear pigs may get swine flu from people.
http://www.alertnet.org/thenews/newsdesk/N30269273.htm. [Last
cited 2009 May 1].
Louise C, Macartney Jane. Man infects pigs with swine flu on farm in
Canada. Times Online. http://www.timesonline.co.uk/tol/news/world/
article6215137.ece. [Last cited on 2009 May 3].
U S l o o k s t o c h a n g e ' s w i n e f l u ' n a m e . A g e n c e Fr a n c e P re s s e . h t t p : / / w w w. g o o g l e . c o m / h o s t e d n e w s / a f p / a r t i c l e /
ALeqM5gBhiP53KpOUE54eBB88rlbMFXfg. Cited on 2009-04-29. [Last
cited on 2009 Apr 29].
Available from: http://www.cdc.gov/h1n1flu/ [Last accessed on 2009
Aug 22].
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
24. South Korea changed the name 'swine flu' to 'Mexican virus'. BCC
(Taiwan)..http://tw.news.yahoo.com/article/url/d/a/090429/1/1imtp.
html. [Last cited on 2009 Apr 29].
25. Renamed swine flu certain to hit Taiwan. The China Post. http://www.
chinapost.com.tw/health/infectiousdiseases/2009/04/29/206057/p2/
Renamed-swine.htm. [Last cited on 2009 Apr 29].
26. Bradsher K. The naming of swine flu, a curious matter. New York Times.
Cited on 2009-04-29. http://www.nytimes.com/2009/04/29/world/
asia/29swine.html. [Last cited on 2009 Apr 28].
27. Pilkington Ed. What's in a name? Governments debate 'swine flu' versus
'Mexican' flu. The Guardian. http://www.guardian.co.uk/world/2009/
apr/28/mexican-swine-flu-pork-name. Cited on 2009-04-29. [Last cited
on 2009 Apr 28].
28. Epidemic and pandemic alert and response (EPR). World Health
Organization. http://www.who.int/csr/disease/swineflu/en/index.html.
[Last cited on 2009 May 1].
29. World Health Organization. Joint FAO/WHO/OIE statement on
influenza A(H1N1) and the safety of pork. Press release. Cited on
2009-05-01. http://www.who.int/mediacentre/news/statements/2009/
h1n1_20090430/en/index.html. [Last cited on 2009 Apr 30].
30. WHO changes swine flu name to 'H1N1 influenza', 257 confirmed cases.
DPA. Hindustan Times. 2009.
31. http://www.hindustantimes.com/StoryPage/StoryPage.aspx?sectionNa
me=Cricketandid=763ce0b9-923f-445b-bdd8-e31fb051270a. [Cited
on 2009 May 2].
32. Not swine nor Mexican, the WHO baptises the flu with 'H1 (in
Spanish). Madrid: ABC Periódico Electrónico. 1 May 2009.http://
www.abc.es/20090501/nacional-sociedad/porcina-mexicana-bautizagripe-20090501.html. [Cited on 2009 May 2].
33. Name dilemma: Swine flu or Mexican flu?. IndiaTimes. http://
timesofindia.indiatimes.com/India/Name-dilemma-Swine-flu-orMexican-flu/articleshow/4464770.cms. [Last cited on 2009 Apr 30].
34. Update: infections with a swine-origin influenza A (H1N1) virus --United States and other countries. Morbidity and Mortality Weekly
Report (U.S. Centers for Disease Control). http://www.cdc.gov/mmwr/
preview/mmwrhtml/mm58d0428a2.htm. [Last cited on 2009 Apr 30].
35. Borenstein Seth. Swine flu name change? Flu genes spell pig.
Associated Press. http://news.yahoo.com/s/ap/20090501/ap_on_he_me/
med_swine_flu_name_13. [Last cited on 2009 Apr 30].
36. Centers for Disease Control And prevention (CDC), Emergence of H5N1
Influenza virus and control options.
37. Kawaoka Y. Influenza Virology: Current Topics. Caister Academic
Press. ISBN 978-1-904455-06-6. http://www.horizonpress.com/flu.2006.
38. H1N1 Influenza (Flu) portal at the U.S. Centers for Disease Control (CDC)
39. H1N1 Influenza Virus - CDC Workplace (NIOSH)
40. Influenza A(H1N1) at the European Centre for Disease Prevention and
Control (ECDC)
41. Heinen PP. Swine influenza: a zoonosis. Veterinary Sciences Tomorrow.
ISSN 1569-0830. Influenza B and C viruses are almost exclusively
isolated from man, although influenza C virus has also been isolated
from pigs and influenza B has recently been isolated from seals. http://
www.vetscite.org/publish/articles/000041/print.html. [Last cited on
2003 Sept 15].
42. Bouvier NM, Palese P. The biology of influenza viruses. Vaccine 26 Suppl
4: D49–53. PMID 19230160. 2008.
43. Kimura H, Abiko C, Peng G, Muraki Y, Sugawara K, Hongo S, et al.
Interspecies transmission of influenza C virus between humans and
pigs. Virus Res 1997;48:71–9.
44. Matsuzaki Y, Sugawara K, Mizuta K, Tsuchiya E, Muraki Y, Hongo S, et
al. Antigenic and genetic characterization of influenza C viruses which
caused two outbreaks in Yamagata City, Japan, in 1996 and 1998. J Clin
Microbiol 2002;40:422-9.
45. Lynch JP 3rd, Walsh EE. Influenza: evolving strategies in treatment and
prevention. Semin Respir Crit Care Med 2007;28:144-58.
46. Swine Influenza. Swine Diseases (Chest). Iowa State University College
of Veterinary Medicine. http://www.vetmed.iastate.edu/departments/
vdpam/swine/diseases/chest/swineinfluenza/.
47. Shin JY, Song MS, Lee EH, Lee YM, Kim SY, Kim HK, et al. Isolation
and characterization of novel H3N1 swine influenza viruses from pigs
with respiratory diseases in Korea. J Clin Microbiol 2006;44:3923–7.
121
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
48. Ma W, Vincent AL, Gramer MR, Brockwell CB, Lager KM, Janke BH,
et al. Identification of H2N3 influenza A viruses from swine in the United
States. Proc Natl Acad Sci U S A 2007;26:20949-54.
49. Kothalawala H, Toussaint MJ, Gruys E. An overview of swine influenza.
Vet Q 2006;28:46–53.
50. Yassine HM, Al-Natour MQ, Lee CW, Saif YM. Interspecies and
Interspecies and intraspecies transmission of triple reassortant H3N2
influenza A viruses. Virol J 2007;4:129.
51. Morbidity and Mortality Weekly Report Dispatch. U.S. Centers for
Disease Control. http://www.cdc.gov/mmwr/preview/mmwrhtml/
mm58d0421a1.htm. [Last cited on 2009 Apr 21].
52. Wilkinson E. What scientists know about swine flu. BBC News. http://
news.bbc.co.uk/2/hi/health/8028371.stm. [Last cited on 2009 May 1].
53. Knobler S, Mack A, Mahmoud A, Lemon S. The Story of Influenza. The
Threat of Pandemic Influenza: Are We Ready? Workshop Summary
Washington, D.C.: The National Academies Press; 2005. p. 75.
54. Olsen CW. The emergence of novel swine influenza viruses in North
America. Virus Res 2002;10:199-210.
55. Soft evidence and hard sell. New York Times, 1976.
56. Taubenberger JK, Morens DM. 1918 Influenza: the mother of all
pandemics. Emerg Infect Dis 2006;12:15-22.
57. U S. pork groups urge hog farmers to reduce flu risk. Reuters, 2009.
58. Heinen P. Swine influenza: a zoonosis. Vet Sci Tom 2003:1–11.
59. Kay RM, Done SH, Paton DJ. Effect of sequential porcine reproductive
and respiratory syndrome and swine influenza on the growth and
performance of finishing pigs. Vet Rec 1994;135:199-204.
60. Influenza fact sheet. Wkly Epidemiol Rec 2003;78:77-80.
61. Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect
Dis 2006;12:9-14.
62. David Brown. System set up after SARS epidemic was slow to alert
global authorities. Washington Post, 2009.
63. Hsieh YC, Wu TZ, Liu DP, Shao PL, Chang LY, Lu CY, et al. Influenza
pandemics: past, present and future. J Formos Med Assoc 2006;105:1-6.
64. Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, et
al. Avian influenza A (H5N1) infection in humans. N Engl J Med
2005;353:1374–85.
65. Ten things you need to know about pandemic influenza. Wkly
Epidemiol Rec 2005;80:428-31.
66. Taubenberger JK, Morens DM. 1918 Influenza: the mother of all
pandemics. Emerg Infect Dis 2006;12:15-22.
67. Vana G, Westover KM. Origin of the 1918 Spanish influenza virus: a
comparative genomic analysis. Mol Phylogenet Evol 2008;47:1100-10.
68. Antonovics J, Hood ME, Baker CH. Molecular virology: was the 1918
flu avian in origin? Nature 2005;437:889-93.
69. Gaydos JC, Top FH Jr, Hodder RA, Russell PK. Swine influenza a outbreak,
Fort Dix, New Jersey, 1976. Emerg Infect Dis 2006;12:23-8.
70. Schmeck, Harold M. Ford Urges Flu Campaign To Inoculate Entire U S.
The New York Times, 1976.
71. Edsall G. The swine flu affair: decision-making on a slippery disease.
Am J Epidemiol 1979;110:522-4.
72. The Last Great Swine Flu Epidemic, Salon.com, 2009.
73. Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P. Safety
of trivalent inactivated influenza vaccines in adults: background for
pandemic influenza vaccine safety monitoring. Vaccine 2009;27:
2114-20.
74. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré
syndrome. Drug Saf 2009;32:309-23.
75. Influenza / Flu Vaccine. University of Illinois at Springfield. http://www.
uis.edu/healthservices/immunizations/influenzavaccine.html. [Cited
on 2009 April 26].
76. BBC: The World. 2009.
77. McKinney WP, Volkert P, Kaufman J. Fatal swine influenza pneumonia
during late pregnancy. Arch Intern Med 1990;150:213–5.
78. Kimura K, Adlakha A, Simon PM. Fatal case of swine influenza virus in
an immunocompetent host. Mayo Clin Proc 1998;73:243-5.
79. Key Facts About Swine Flu (CDC). Cdc.gov. http://www.cdc.gov/swineflu/
key_facts.htm. [Cited on 2009 May 7].
80. Wells DL, Hopfensperger DJ, Arden NH, Harmon MW, Davis JP, Tipple
MA, et al. Swine influenza virus infections. Transmission from ill pigs
to humans at a Wisconsin agricultural fair and subsequent probable
122
person-to-person transmission. JAMA 1991;265:478-81.
81. Desmon S. Expert: Swine flu virus more complex than typically seen.
Baltimore Sun. http://www.baltimoresun.com/news/health/bal-swineflu-strain0428,0,3165467.story. [Last cited on 2009 Apr 28].
82. Pork industry is blurring the science of swine flu - Short Sharp
Science. New Scientist. http://www.newscientist.com/blogs/
shortsharpscience/2009/04/why-the-pork-industry-hates-th.html.
[Cited on 2009 May 7].
83. Swine flu. The predictable pandemic? New Scientist. http://www.
newscientist.com/article/mg20227063.800-swine-flu-the-predictablepandemic.html? full=true. [Cited on 2009 May 7].
84. DA probes reported swine flu 'outbreak' in N. Ecija. Gmanews.tv. http://
www.gmanews.tv/story/56805/DA-probes-reported-swine-flu-outbreakin-N-Ecija. [Cited on 2009 Apr 25].
85. Gov't declares hog cholera alert in Luzon. Gmanews.tv. http://www.
gmanews.tv/story/53014/Govt-declares-hog-cholera-alert-in-Luzon.
[Cited on 2009 Apr 25].
86. Maria Zampaglione. Press Release: A/H1N1 influenza like human
illness in Mexico and the USA: OIE statement. World Organisation for
Animal Health. http://www.oie.int/eng/press/en_090427.htm. [Cited
on 2009 Apr 29].
87. Outbreak of swine-origin influenza A (H1N1) virus infection - Mexico.
MMWR Morb Mortal Wkly Rep 2009;58:467-70.
88. Kahn LH. Stirring up swine flu hysteria. Bulletin of the Atomic Scientists.
http://thebulletin.org/web-edition/columnists/laura-h-kahn/stirringswine-flu-hysteria. [Last cited on 2009 May 11]
89. An Alberta Swine Herd Investigated for H1N1 Flu Virus. The Canadian
Food Inspection Agency. http://www.inspection.gc.ca/english/corpaffr/
newcom/2009/20090502e.shtml. [Cited on 2009 May 3].
90. World takes drastic steps to contain swine flu. http://news.yahoo.
com/s/ap/20090430/ap_on_he_me/eu_swine_flu_drastic_measur es.
[Cited on 2009 Apr 30].
91. swine flu outbreak. From Wikipedia, the free encyclopedia. 2009.
92. A look at Illinois swine flu cases. Associated Press. Chicago
Tribune. http://www.chicagotribune.com/news/chi-ap-il-swinefluillinois,0,3135647.story. [Cited on 2009 May 13].
93. CDC Telebriefing on Investigation of Human Cases of H1N1 Flu May
15, 2009. U.S. Centers for Disease Control and Prevention. http://www.
cdc.gov/media/transcripts/2009/t090515.htm. [Cited on 2009 May 21].
94. Mexico: Number of new swine flu cases stabilizing. Associated
P r e s s . h t t p : / / w w w. g o o g l e . c o m / h o s t e d n e w s / a p / a r t i c l e /
ALeqM5gfYcVCw5PiKbk5yaX7JaF9NqhPygD97SVQV02. [Cited on
2009 Apr 30].
95. Wayne T. Province told to stop talking about suspected flu
cases. The Guardian. http://www.theguardian.pe.ca/index.
cfm?sid=247322andsc=98. [Cited on 2009 May 5].
96. Situation updates - Influenza A(H1N1). Epidemic and Pandemic Alert
and Response. WHO. http://www.who.int/csr/disease/swineflu/updates/
en/index.html. [Cited on 2009 May 13] .
97. Influenza Factsheet. Center for Food Security and Public Health,
Iowa State University. http://www.cfsph.iastate.edu/Factsheets/pdfs/
influenza.pdf.
98. Gilchrist MJ, Greko C, Wallinga DB, Beran GW, Riley DG, Thorne PS. The
potential role of concentrated animal feeding operations in infectious
disease epidemics and antibiotic resistance. Environ Health Perspect
2007;115:313-6.
99. Saenz RA, Hethcote HW, Gray GC. Confined animal feeding operations
as amplifiers of influenza. Vector Borne Zoonotic Dis 2006;6:338-46.
100. Vicente J, León-Vizcaíno L, Gortázar C, José Cubero M, González M,
Martín-Atance P. Antibodies to selected viral and bacterial pathogens in
European wild boars from southcentral Spain. J Wildl Dis 2002;38:64952.
101. Gray GC, Kayali G. Facing pandemic influenza threats: the importance
of including poultry and swine workers in preparedness plans. Poult
Sci 2009;88:880-4.
102. Gray GC, Trampel DW, Roth JA. Pandemic influenza planning: shouldn't
swine and poultry workers be included? Vaccine 2007;25:4376-81.
103. Gray GC, McCarthy T, Capuano AW, Setterquist SF, Olsen CW, Alavanja
MC. Swine workers and swine influenza virus infections. Emerg Infect
Dis 2007;13:1871-8. Myers KP, Olsen CW, Setterquist SF, Capuano AW,
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
104.
105.
106.
107.
108.
109.
110.
111.
112.
113.
114.
115.
116.
117.
118.
119.
120.
121.
122.
123.
124.
125.
126.
127.
128.
129.
Donham KJ, Thacker EL, et al. Are swine workers in the United States
at increased risk of infection with zoonotic influenza virus? Clin Infect
Dis 2006;42:14-20.
Thacker E, Janke B. Swine influenza virus: zoonotic potential and
vaccination strategies for the control of avian and swine influenzas. J
Infect Dis 2008;197:19-24.
Yu H, Hua RH, Zhang Q, Liu TQ, Liu HL, Li GX. Genetic evolution of
swine influenza A (H3N2) viruses in China from 1970 to 2006. J Clin
Microbiol 2008;46:1067-75.
Lindstrom SE, Cox NJ, Klimov A. Genetic analysis of human H2N2
and early H3N2 influenza viruses, 1957-1972: evidence for genetic
divergence and multiple reassortment events. Virology 2004;328:
101-19.
World Health Organization. H5N1 avian influenza: timeline (PDF).
http://www.who.int/csr/disease/avian_influenza/Timeline_28_10a.pdf.
[Cited on 2005 May 28].
Indonesian pigs have avian flu virus; bird cases double in China.
University of Minnesota: Center for Infectious Disease Research and
Policy. http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/
news/may2705avflu.html. [Cited on 2009 Apr 26].
H5N1 virus may be adapting to pigs in Indonesia. University of
Minnesota: Center for Infectious Disease Research and Policy.
http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/
mar3109swine-jw.html. [Cited on 2009 Apr 26].
UK Health Protection Agency. Information for the media on face masks.
Press release. http://www.hpa.org.uk/web/HPAwebandHPAwebStandard/
HPAweb_C/1240899135838. [Cited on 2009 Apr 28].
Joint FAO/WHO/OIE Statement on influenza A(H1N1) and the safety
of pork. 2009.
What to Do If You Get Flu-Like Symptoms. Centers for Disease Control
and Prevention. 2009-05-07. http://www.cdc.gov/h1n1flu/sick.htm.
[Cited on 2009 May 22].
About the disease. World Health Organization. http://www.who.int/csr/
disease/swineflu/frequently_asked_questions/about_disease/en/index.
html. [Cited on 2009 May 22] .
New York City officials struggle for balanced response to swine flu,
Los Angeles Times.2009.
Spread of Swine Flu Puts Japan in Crisis Mode, New York Times.2009.
Japanese Schools Reopen as Swine Flu Threat Abates Bloomberg
News.2009.
Mexico City ends swine flu alert, no cases in week Associated
Press.2009.
Centers for Disease Control and Prevention > Key Facts about Swine
Influenza (Swine Flu). http://www.cdc.gov/swineflu/key_facts.htm.
[Cited on 2009 Apr 27].
Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a
review of the literature. Clin Infect Dis 2007;44:1084-8.
Swine Flu and You. CDC. 2009. http://www.cdc.gov/swineflu/swineflu_
you.htm. [Cited on 2009].
Centers for Disease Control and Prevention. CDC Health Update:
Swine Influenza A (H1N1) Update: New Interim Recommendations
and Guidance for Health Directors about Strategic National Stockpile
Materiel. Health Alert Network. http://www.cdc.gov/swineflu/
HAN/042609.htm. [Cited on 2009 Apr 27].
WHO chief warns H1N1 swine flu likely to worsen Intellasia, 2009.
New virus very unstable, more changes seen-expert, Reuters, 2009.
Baylor College and Medical News Today. Avian Flu Virus Freed From
Immune Recognition By Protein 'Tubules'. Medical News Today. http://
www.medicalnewstoday.com/articles/128419.php. [Cited on 2008
Nov 11].
WHO Pandemic Influenza Phases. World Health Organization. http://
www.who.int/csr/disease/avian_influenza/phase/en/index.html. [Cited
on 2009 Apr 27].
Scientists See This Flu Strain as Relatively Mild, Los Angeles Times,
2009.
WHO to consider severity of 'sneaky' swine flu AP, 2009.
Swine Flu Is Spreading More Widely Than Official Numbers Show
Bloomberg News, 2009.
Swine flu virus turns endemic. National Hog Farmer. http://
nationalhogfarmer.com/mag/swine_flu_virus_endemic/. [Cited on
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2
2007 Sept 15].
130. Swine. Custom Vaccines. Novartis. http://www.livestock.novartis.com/
cv_swine.html.
131. Gramer MR, Lee JH, Choi YK, Goyal SM, Joo HS. Serologic and genetic
characterization of North American H3N2 swine influenza A viruses.
Can J Vet Res 2007;71:201-6.
132. Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a
review of the literature. Clin Infect Dis 2007;44:1084-8.
133. Swine flu. The predictable pandemic? http://www.newscientist.com/
article/mg20227063.800-swine-flu-the-predictable-pandemic.html?
full=true/. [Cited on 2009 Apr 29].
134. Ramirez A, Capuano AW, Wellman DA, Lesher KA, Setterquist SF, Gray
GC. Preventing zoonotic influenza virus infection. Emerg Infect Dis
2006;12:996-1000.
135. Q and A. Key facts about swine influenza (swine flu) – Spread of Swine
Flu. Centers for Disease Control and Prevention, 2009.
136. Q and A. Key facts about swine influenza (swine flu) – Diagnosis. Centers
for Disease Control and Prevention, 2009. http://www.cdc.gov/swineflu/
key_facts.htm. [Cited on 2009 Apr 26].
137. CDC - Influenza (Flu) | Swine Influenza (Flu) Investigation. Cdc.gov.
http://cdc.gov/swineflu/investigation.htm. [Cited on 2009 Apr 27].
138. Chlorine Bleach: Helping to Manage the Flu Risk. Water Quality and
Health Council. http://www.waterandhealth.org/newsletter/new/
winter_2005/chlorine_bleach.html. [Cited on 2009].
139. Q and A. Key facts about swine influenza (swine flu) – Virus Strains.
Centers for Disease Control and Prevention, 2009. http://www.cdc.gov/
swineflu/key_facts.htm. [Cited on 2009 Apr 26].
140. Petty L. Swine Flu Vaccine Could Be Ready in 6 Weeks. NBC Connecticut.
http://www.nbcconnecticut.com/news/local/CT-Company-MakingSwine-Flu-Vaccine.html. [Cited on 2009 Apr 28].
141. www.who.int/csr/disease/swineflu/faq/en/index.html. http://www.who.
int/csr/disease/swineflu/faq/en/index.html.
142. Antiviral Drugs and Swine Influenza. Centers for Disease Control. http://
www.cdc.gov/swineflu/antiviral_swine.htm. [Cited on 2009 Apr 27].
143. ''FDA Authorizes Emergency Use of Influenza Medicines, Diagnostic
Test in Response to Swine Flu Outbreak in Humans.'' FDA News, April
27, 2009. Fda.gov. 2009. http://www.fda.gov/bbs/topics/NEWS/2009/
NEW02002.html. [Cited on 2009 May 7].
144. H1N1 flu (swine flu). Centers for Disease Control and Prevention.. http://
www.cdc.gov/h1n1flu/. [Cited on 2009 May 7].
145. Bleach C. Helping to Manage the Flu Risk. Water Quality and Health
Council. http://www.waterandhealth.org/newsletter/new/winter_2005/
chlorine_bleach.html. [Cited on 2009 May 12].
146. Warning against buying flu drugs online. The Guardian. http://www.
guardian.co.uk/lifeandstyle/besttreatments/2009/may/08/warningagainst-buying-flu-drugs-online. [Cited on 2009 May 8].
147. Janice L. New swine flu concern going forward: drug resistance. USA
Today. http://www.usatoday.com/news/health/2009-05-05-tamifluswine-resistance_N.htm. [Cited on 2009 May 11].
148. Butler D. Marie-Paule Kieny. Nature News. http://www.nature.com/
news/2009/090513/full/news.2009.478.html. [Cited on 2009 May 14]
149. Wu JT, Leung GM, Lipsitch M, Cooper BS, Riley S. Hedging against
antiviral resistance during the next influenza pandemic using small
stockpiles of an alternative chemotherapy. PLoS Med 2009;6:1000085.
150. Waters R. Relenza Should Be First Flu Drug Used, Study Says (Update1).
http://www.bloomberg.com/apps/news?pid=20601124andsid=adAvv
B1lod_sandrefer=home. [Cited on 2009 Apr 30]
151. Antiviral Agents for Seasonal Influenza: Side Effects and Adverse
Reactions.
152. Harper SA, Bradley JS, Englund JA, File TM, Gravenstein S, Hayden FG,
et al. Seasonal influenza in adults and children-diagnosis, treatment,
chemoprophylaxis, and institutional outbreak management: clinical
practice guidelines of the Infectious Diseases Society of America. Clin
Infect Dis 2009;48:1003-32.
153. Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G,
Prevention and control of influenza: recommendations of the Advisory
Committee on Immunization Practices (ACIP), 2008. MMWR Recomm
Rep 2008;57:1-60.
154. prophylaxis, and Institutional Outbreak Management: Clinical Practice
123
Gangurde, et al.: Swine Influenza A (H1N1 Virus)
Guidelines of the Infectious Diseases Society of America.
155. Swine Flu. Emergency Use Authorization (EUA) of Medical Products
and Devices.
156. Postnote published by Parliamentry office of Science and Technology
on H1N1 ‘Swine flu’ vaccine. 2009.
157. http://en.wikipedia.org/wiki/2009_swine_flu_outbreak
158. Montalto NJ, Gum KD, Ashley JV. Updated treatment for influenza A
and B. Am Fam Physician 2000;62:2467-76.
159. Taking Care of Yourself: What to Do if You Get Sick with Flu. Disease
and Conditions: Seasonal Flu. CDC. 2008-02-06. http://www.cdc.gov/
flu/takingcare.htm. [Cited on 2008 Oct 24].
160. Nicole SM, Bresee JS, Shay DK, Uyeki TM, Cox NJ, Strikas RA. Prevention
and Control of Influenza: Recommendations of the Advisory Committee
124
on Immunization Practices (ACIP). Morbidity and Mortality Weekly
Report. Centers for Disease Control and Prevention. http://www.cdc.
gov/mmwr/preview/mmwrhtml/rr5510a1.htm. [Cited on 2007 May 25].
161. Cold and Flu Guidelines: Influenza. American Lung Association. http://
www.lungusa.org/site/pp.asp?c=dvLUK9O0Eandb=35868. [Cited on
2007 Sept 16].
Cite this article as: Gangurde HH, Gulecha VS, Borkar VS, Mahajan MS,
Khandare RA, Mundada AS. Swine Influenza A (H1N1 Virus): A pandemic
disease. Syst Rev Pharm 2011;2:110-24.
Source of Support: Nil, Conflict of Interest: None declared.
Systematic Reviews in Pharmacy | July-December 2011 | Vol 2 | Issue 2